The long-range goal of this research is to control or regulate the loss of nitrogen and wasting complications associated with diabetes and several other diseases. One aspect of this research involves establishing how hormones, or the lack of certain hormones, influence the process of intracellular protein catabolism in particular tissues. In this proposed project the consequences of chemically-induced diabetes on the rates of degradation of a sppctrum of intracellular proteins and two specific enzymes in mouse muscle and liver will be assessed. More specifically, we will determine the effects of alloxan- and streptozotocin-induced diabetes and a) the overall rate of degradation (half-lives) of supernatant and particulate proteins in mouse muscle and liver, b) the degradation of small groups or individual proteins separated chromatographically and electrophoretically from supernatant fractions, and c) the degradation of two specific enzymes present in liver and muscle: glyceraldehyde-phosphate dehydrogenase and alanine aminotransferase. In addition, we plan to determine whether administration of insulin to diabetic mice reverses the effects of diabetes on protein degradation and whether the administration of glucagon to diabetic mice exaggerates the effects of diabetes on protein turnover. The results of the proposed research should establish definitively whether the negative nitrogen balance observed in diabetic animals is due to accelerated protein degradation and whether proteins are affected differentially.